Lunasin is a 43 amino acid small subunit of a soybean 2S albumin. The polynucleotide encoding the lunasin peptide, and the peptide sequence of lunasin are known and disclosed in U.S. Pat. No. 6,544,956 (hereby incorporated by reference in its entirety) in which the lunasin peptide is encoded by bases 80-208 of SEQ ID NO:1, and the peptide is defined by residues 22-64 of SEQ ID NO:2. The carboxyl end of lunasin contains a chromatin-binding domain, a cell adhesion motif Arg-Gly-Asp (RGD) followed by eight Asp residues (Galvez and de Lumen, 1997; Galvez and de Lumen, 1999). The chromatin-binding domain consists of a 10-amino acid helical region homologous to a short conserved region found in other chromatin binding proteins (Aasland and Stewart, 1995). Mammalian studies provide evidence that lunasin may play a role in the cell cycle control (Galvez and de Lumen, 1999; Galvez et al., 2001; Jeong et al., 2002). For example, transfection of the lunasin gene into mammalian cells results in mitotic arrest and subsequent cell death (Galvez and de Lumen, 1999). In addition, exogenous addition of chemically synthesized lunasin to mammalian cells demonstrates that lunasin colocalizes with hypoacetylated chromatin; preferentially binds deacetylated histone H4 in vitro; and prevents histone H3 and H4 acetylation in vivo in the presence of a histone deacetylase inhibitor (Galvez et al., 2001). Acetylation and deacetylation of conserved histone N-terminal tails result in chromatin conformational changes that induce or suppress gene expression. It has been hypothesized that Lunasin modulates changes in chromatin organization by modifying histone tails, thereby, affecting gene expression that produces its anti-neoplastic properties. Recently, lunasin was isolated from barley and was reported to possess the same biological activity ascribed to chemically synthesized lunasin (Jeong et al., 2002).
Lunasin peptide has been shown to have anti-neoplastic properties (Galvez et al., 2001). Significant suppression of chemical carcinogen-induced, e.g. 7,12-dimethylbenz-[a]-anthracene (DMBA) and 3-methylcholanthrene (MCA), foci formation in C3H 10T1/2 mouse embryo fibroblast cells was observed when lunasin was added exogenously at nanomolar concentrations. In addition, topical application of lunasin inhibited skin tumorigenesis in female SENCAR mice. Lunasin peptide has also been shown to induce apoptosis in E1A-transfected C3H10T1/2 cells (Galvez et al., 2001) and suppress foci formation in E1A-transfected mouse fibroblast NIH 3T3 cells (Lam, et al., in press). E1A is a viral onco-protein that inactivates the Rb (retinoblastoma) tumor suppressor (Nevins, 1992). Furthermore, when C3H 10T1/2 and MCF-7 human breast cancer cells were treated with lunasin in the presence of the histone deacetylase inhibitor, sodium butyrate, a 10- to 95-fold reduction in acetylation of core histones H3 and H4 was observed (Galvez et al., 2001). The genome-wide reduction in core histone acetylation suggests an epigenetic mechanism of action for lunasin that can influence gene expression fundamental to carcinogenesis.